Natural Product: NPC300593

Natural Product IDNPC300593
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5E,10(14)-Germacradien-1Beta,4Beta-Diol
IUPAC Name (1S,4S,5E,7S)-4-methyl-10-methylidene-7-propan-2-ylcyclodec-5-ene-1,4-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL513802
PubChem CID 44567152
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids
          • [CHEMONTID:0002456] Germacrane sesquiterpenoids

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey NSIOXFVMCTYIOU-UVIYIIQCSA-N
Standard InCHI InChI=1S/C15H26O2/c1-11(2)13-6-5-12(3)14(16)8-10-15(4,17)9-7-13/h7,9,11,13-14,16-17H,3,5-6,8,10H2,1-2,4H3/b9-7+/t13-,14+,15-/m1/s1
SMILES CC(C)[C@@H]1CCC(=C)[C@H](CC[C@@](C)(/C=C/1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   238.19 Volume:   271.747
?
Van der Waals volume.
Dense:   0.877 LogP:   2.712
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.755
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.64
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   11.0
TPSA:   40.46
?
Topological Polar Surface Area.
 H-Bond Acceptor:   2.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   2.0

MedChem Properties

QED Drug-Likeness Score:   0.689 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.596 Fsp3:   0.733
MCE-18:   25.385
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.224 Fluc inhibitor:   0.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.003
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.016
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.953 Promiscuous compounds:   0.273

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.745 MDCK Permeability:   -4.66
Pgp-inhibitor:   0.021 Pgp-substrate:   0.378
PAMPA:   0.593
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.0
20% Bioavailability (F20%):   0.125 30% Bioavailability (F30%):   0.27
50% Bioavailability (F50%):   0.903

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.358
Plasma Protein Binding (PPB):   90.877% Volume Distribution (VD):   0.047
Fu: 6.612%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.735
OATP1B3 inhibitor:   0.689 BCRP inhibitor:   0.462
BSEP inhibitor:   0.919

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.09
CYP2C19-inhibitor:   0.393 CYP2C19-substrate:   0.025
CYP2C9-inhibitor:   0.035 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.181
CYP3A4-inhibitor:   0.004 CYP3A4-substrate:   0.02
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.823
HLM stability:   0.941
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  12.018 Half-life (T1/2):  1.777

ADMET: Toxicity

hERG Blockers:  0.037 hERG Blockers (10um):  0.208
Human Hepatotoxicity (H-HT):  0.865 Drug-induced Liver Injury (DILI):  0.164
AMES Toxicity:  0.326 Rat Oral Acute Toxicity:  0.185
Maximum Recommended Daily Dose:  0.652 Skin Sensitization:  0.996
Carcinogencity:  0.699 Eye Corrosion:  0.734
Eye Irritation:  0.986 Respiratory Toxicity:  0.543
Drug-induced Neurotoxicity:  0.434 Ototoxicity:  0.505
Hematotoxicity:  0.415 Drug-induced Nephrotoxicity:  0.888
Genotoxicity:  0.322 RPMI-8226 Immunitoxicity:  0.142
A549 Cytotoxicity:  0.425 Hek293 Cytotoxicity:  0.253
BCF:   1.102
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.323
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.813
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.17
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits Spanish DOI[10.1021/jf00010a019]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. Italy DOI[10.1021/jf00016a013]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. Germany DOI[10.1021/jf00016a013]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. DOI[10.1021/jf00016a013]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits Turkey DOI[10.1111/j.1745-4557.2003.tb00250.x]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. DOI[10.17660/ActaHortic.2003.610.16]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[10794642]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[10820090]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[11754554]
NPO8788 Renealmia nicolaioides Species Zingiberaceae Eukaryota n.a. n.a. n.a. PMID[12444686]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[15315387]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[16076125]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[16920856]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[19358604]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[21190690]
NPO6674 Burkholderia ambifaria Species Burkholderiaceae Bacteria n.a. n.a. n.a. PMID[22988812]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[23394984]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. Germany PMID[23394984]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. New Zealand PMID[23394984]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[2413754]
NPO17386 Securidaca longepedunculata Species Polygalaceae Eukaryota n.a. n.a. n.a. PMID[24216090]
NPO11257 Momordica dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. PMID[30673219]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota Fruits n.a. PMID[9542132]
NPO3385 Cassine transvaalensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11097 Lepidium apetalum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17386 Securidaca longepedunculata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6674 Burkholderia ambifaria Species Burkholderiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO11815 Mikania hirsutissima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3740 Trisetum flavescens Species Poaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19898 Stevia lucida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1185 Stereocaulon strictum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12998 Salvia rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7345 Ptilonia magellanica Species Bonnemaisoniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11555 Pterocaulon purpurascens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16164 Podocarpus urbani Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO936 Pinalia spicata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9512 Phlomis fruticosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5392 Pachycereus pecten-aboriginum Species Cactaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11257 Momordica dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12891 Minasia alpestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8788 Renealmia nicolaioides Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10399 Manfreda virginica Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5013 Loranthus spicatus Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9307 Ficus indica Species Ficidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6256 Eucalyptus umbra Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7048 Eucalyptus rariflora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9040 Elsinoe annonae Species Elsinoaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO468 Dryopteris oligophlebia Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5827 Dalea tuberculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10738 Cotoneaster horizontalis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO12192 Coronilla scorpioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8484 Codonopsis lanceolata Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9928 Cephalaria cilicica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11097 Lepidium apetalum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11257 Momordica dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11097 Lepidium apetalum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11097 Lepidium apetalum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11257 Momordica dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11097 Lepidium apetalum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO10399 Manfreda virginica Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16164 Podocarpus urbani Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11815 Mikania hirsutissima Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9040 Elsinoe annonae Species Elsinoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9928 Cephalaria cilicica Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6674 Burkholderia ambifaria Species Burkholderiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO11097 Lepidium apetalum Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9512 Phlomis fruticosa Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3385 Cassine transvaalensis Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3740 Trisetum flavescens Species Poaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6256 Eucalyptus umbra Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5392 Pachycereus pecten-aboriginum Species Cactaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5013 Loranthus spicatus Species Loranthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2300 Actinidia deliciosa Species Actinidiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO936 Pinalia spicata Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7048 Eucalyptus rariflora Species Myrtaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9307 Ficus indica Species Ficidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5827 Dalea tuberculata Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10738 Cotoneaster horizontalis Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11555 Pterocaulon purpurascens Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11257 Momordica dioica Species Cucurbitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12891 Minasia alpestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1185 Stereocaulon strictum Species Stereocaulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO468 Dryopteris oligophlebia Species Dryopteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17386 Securidaca longepedunculata Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19898 Stevia lucida Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12998 Salvia rubescens Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12192 Coronilla scorpioides Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7345 Ptilonia magellanica Species Bonnemaisoniaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8484 Codonopsis lanceolata Species Campanulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8788 Renealmia nicolaioides Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



  NP Quantity Composition/Concentration

Organism ID Organism Name Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].



 Biological Activity

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 < 5.0 ug.mL-1 PMID[12444686]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC300593 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.5897 Remote Similarity NPC225342
0.561 Remote Similarity NPC488047
0.55 Remote Similarity NPC68014

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC300593 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data